Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04626 (erbB-2)
 5,251 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

With the breast carcinoma cell line BT 474 used as a source of antigen, four rat monoclonal antibodies (MAbs) (3 IgG2a and I IgA) have been prepared against the external domain of the product of the c-erbB-2 proto-oncogene. All 4 antibodies stain frozen sections of tissues that over-express the product of the c-erbB-2 proto-oncogene, and competitive binding assays showed that the antibodies recognized 2 non-overlapping epitopes. Representative antibodies from the two groups (ICR12 and 13) were shown to specifically immunoprecipitate a 190 kDa protein from 35S-methionine-labelled breast carcinoma cells where the c-erbB-2 is amplified (BT 474 and MDA-MB 361). Two of the antibodies (ICR12 and ICR17) bind to the denatured antigen in Western blots and ICR12 stains formolsaline-fixed sections of breast carcinoma tissue that over-expresses the product of the c-erbB-2 proto-oncogene. These antibodies should be useful not only for immunocytochemical diagnoses but also for radio-immunoscintigraphic and therapeutic applications.
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PMID:Rat monoclonal antibodies to the external domain of the product of the C-erbB-2 proto-oncogene. 168 75

Recently cervical cancer is defined as a sexually-transmitted disease, and human papillomavirus (HPV) has been focused as one of its etiologic agents. It is known that cervical cancer is extraordinarily rare in non-human mammals that have the estrous cycle. In contrast, cervical cancer is frequent in human beings which have lost the estrous cycle, and subsequently evolved a sexual behavior irrespective of the menstrual phase. Therefore, upon the hypothesis that the estrous cycle is a period protected from a sexually transmitted disease, we studied the status of local defence mechanism and growth/differentiation of normal cervical epithelium during the menstrual cycle and pregnancy. Then, the influence of HPV-infection on the growth and differentiation of cervical epithelium was analyzed. As a local immune system of the cervix, both IgA and IgG are secreted in the cervical mucus, and the levels in the follicular phase were significantly higher than those during the luteal phase and pregnancy. An existence of local defence mechanism in the follicular phase is suggested. Analysis of a cell proliferation antigen Ki-67 in normal cervix revealed that parabasal cells enter the cell cycle more frequently in the luteal phase than in the follicular phase. Basal and reserve cells are usually resting, but a few cells enter the cell cycle during the luteal phase and during pregnancy. Since cycling cells are more susceptible to viral infection, the basal and/or reserve cells during the luteal phase and pregnancy are suggested to be under the risk for HPV infection. As factors regulating growth and differentiation of cervical squamous epithelium, immunohistochemical expression of estrogen receptor (ER), progesterone receptor (PR), epidermal growth factor receptor (EGFR), c-erbB-2 protein, adult T-cell leukemia-derived factor (ADF), and HPV DNA was examined. In normal cervix, basal cells were usually ER-positive and PR-negative. Parabasal cells were ER-positive and PR-negative in the follicular phase, while they were ER-negative and PR-positive during the luteal phase and pregnancy. Considering the results of Ki-67 expression, the ER-negative and PR-positive status is possibly related to the proliferation of the cervical squamous epithelium. In cervical condylomas, basal cells infected by HPV6/11 were ER-positive, but HPV16/18-infected cells were ER-negative. Neoplastic cells of CINs and invasive squamous carcinomas containing HPV DNA 16/18 were ER-negative, while those containing HPV DNA 31/33/35 were weakly ER-positive. PR was positive in 2 of 2 condylomas, 18 of 26 CINs, and 13 of 22 invasive carcinomas.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Studies on pathogenesis of cervical carcinoma based on the analysis of growth and differentiation mechanism of cervical epithelium]. 217 18

Using the breast carcinoma cell line MDA-MB 468 as immunogen, we have produced six new rat monoclonal antibodies (mAbs) against the human EGF receptor (EGFR) and are investigating their use for diagnostic and therapeutic applications in cancer patients whose tumours overexpress these receptors. The mAbs (three IgG2b and one each of IgG2a, IgG1 and IgA) were selected on the basis that they bound to the extracellular domain of the EGFR and blocked growth factor-receptor interaction. Competitive assays showed that, with the exception of antibody ICR65, the mAbs bound to one of two distinct epitopes on the external domain of the EGFR. ICR65, however, cross-reacted with mAbs binding to both epitopes. All of the mAbs immunoprecipitated the 170 kDa glycoprotein from cells expressing the EGFR but not the 185 kDa product of the related c-erbB-2 proto-oncogene. Unlike EGF and TGF alpha none of the mAbs stimulated the growth of quiescent human foreskin fibroblasts but they inhibited the EGF and TGF alpha induced growth stimulation of these cells in vitro. When tested for their effect on tumour cells the mAbs were found to inhibit the growth in vitro of a number of human tumours that overexpressed the EGFR (e.g. HN5, HN6, HN15, A431, MDA-MB 468) but they were without effect on tumour cell lines expressing low or undetectable amounts of the receptor. Our initial results indicate that this new generation of antibodies which bind with high affinity to the EGFR, block growth factor-receptor interaction and inhibit the growth of human squamous carcinoma cell lines overexpressing the receptor have potential for clinical application.
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PMID:The human EGF receptor as a target for cancer therapy: six new rat mAbs against the receptor on the breast carcinoma MDA-MB 468. 809 90

Promising results from clinical trials with unconjugated antibodies stimulated renewed interest in immune effector mechanisms of monoclonal antibodies (MoAbs). We investigated the potential of IgA as antibody isotype for cell- or complement-mediated tumor cell lysis and assessed the potential of its myeloid Fc receptor, FcalphaRI (CD89), as trigger molecule for bispecific antibody (BsAb)-mediated immunotherapy. Comparing hapten-directed antibodies of human IgA2 with IgG1 or IgG3 isotypes, we found all three to mediate effective killing of sensitized tumor target cells in whole blood assays. Analysis of effector mechanisms showed IgG-mediated lysis to be predominantly complement-dependent, whereas IgA-dependent killing was primarily effector cell-mediated. A comparison of effector cell populations in antibody-dependent cell-mediated cytotoxicity (ADCC) showed neutrophils to be most important for IgA-dependent tumor cell killing, involving FcalphaRI as shown with Fc receptor blocking antibodies. Reverse ADCC experiments against target cells sensitized with Fc receptor antibodies, or assays with FcalphaRI-directed bispecific antibodies confirmed FcalphaRI as effective trigger molecule in polymorphonuclear neutrophil (PMN)-mediated lysis. During granulocyte colony-stimulating factor (G-CSF ) therapy, (FcalphaRI x HER-2/neu) bispecific antibodies induced enhanced killing of HER-2/neu positive SK-BR-3 breast cancer cells in whole blood assays. This enhanced cytotoxicity was paralleled by increased PMN counts, which lead to higher effector to target cell ratios in G-CSF-primed blood. Furthermore, bispecific antibodies, directed to FcalphaRI and Candida albicans, enhanced neutrophils' phagocytosis of fungi. In summary, these results identify IgA as an effective antibody isotype for immunotherapy, working primarily via FcalphaRI on neutrophils. They suggest FcalphaRI-directed bispecific antibodies and G-CSF to be an attractive combination for malignant or infectious diseases.
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PMID:FcalphaRI (CD89) as a novel trigger molecule for bispecific antibody therapy. 937 59

The HER-2/neu protein is overexpressed in approximately 20% of human adenocarcinomas and is a defined tumor antigen in breast cancer. The purpose of this study was to evaluate the endogenous HER-2/neu specific antibody response in 57 patients with colorectal cancer. HER-2/neu specific antibodies, titer > or = 1:100, were detected in 14% (8/57) of patients with colorectal cancer compared to none of the normal control population (0/200). Furthermore, detection of HER-2/neu specific antibodies in the cancer population correlated significantly with HER-2/neu protein overexpression in the patients' tumor (p < 0.01). 46% of patients with HER-2/neu overexpressing tumors (6/13) and 5% of HER-2/neu negative tumors (2/44) had detectable HER-2/neu specific antibodies. The endogenous HER-2/neu antibody response in these patients was predominantly IgG or IgA.
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PMID:Antibody immunity to the HER-2/neu oncogenic protein in patients with colorectal cancer. 1040

Recent studies in HER-2/neu-targeted immunotherapy demonstrated that polymorphonuclear neutrophils (PMN) mediated Ab-dependent cellular cytotoxicity against HER-2/neu-positive breast cancer cell lines. However, the mechanism of cell death remained unclear. We used several assays to analyze the induction of apoptosis in the breast cancer cell line SK-BR-3 via PMN-dependent Ab-dependent cellular cytotoxicity. In the presence of the HER-2/neu Ab 520C9 and PMN from healthy donors, apoptosis occurred as detected by annexin V binding and disappearance of euploid SK-BR-3 nuclei, which can be differentiated from PMN nuclei by their increased DNA contents. Apoptosis induction was observed with E:T cell ratios as low as 10:1. Laser scanning fluorescence microscopy of TUNEL tumor cells or staining for cleaved cytokeratin-18 further confirmed apoptosis of the SK-BR-3 breast cancer cells. Killing via 520C9 was dependent on the interaction with FcR on PMN, because 1) F(ab')(2) fragments of 520C9 mediated no cytotoxicity, 2) target cell death was influenced by a biallelic polymorphism of FcgammaRIIa on the effector cells, and 3) a bispecific Ab against HER-2/neu and the IgA receptor (FcalphaRI) expressed on effector cells significantly induced apoptosis. Thus, PMN induce Ab-dependent apoptosis against human breast cancer cells targeted with HER-2/neu-directed mAbs or FcR directed bispecific Abs.
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PMID:Polymorphonuclear granulocytes induce antibody-dependent apoptosis in human breast cancer cells. 1460 11